In the laboratory, work will be addressed to three endogenous neuropeptides, oxytocin (OXY), neurotensin (NT) and thyrotropin-releasing hormone (TRH). Work with OXY will focus on the property of this peptide to produce maternal behavior in virgin female rats. Interest is now focused on blocking the action of endogenous OXY in triggering this behavior in a variety of circumstances. Neurotensin is of interest because many of its actions run parallel to those of neuroleptic drugs. We propose to identify the sites in brain where NT enhances pentobarbital-induced sleeping time and where it enhances pentobarbital-induced hypothermia. Additional studies bear upon the role of NT in thermoregulation. While NT prolongs pentobarbital-induced sleeping time, TRH shortens it. We will use this property of TRH to study the action of putative inhibitors of TRH synthesis and inhibitors of TRH degradation. Additional studies are addressed to probable interactions between TRH and NT. In the clinic, work will focus on three endogenous peptides: NT, TRH, and insulin. Because NT can blunt the TSH response to TRH it will be of interest to discern whether patients with blunted responses have altered levels of NT in spinal fluid. The TSH response to TRH will also be studied as regards its characteristics in a large population of normals and its possible influence by stage of the menstrual cycle. Its possible value in predicting the efficacy of L-triiodothyronine as an adjunct to imipramine in depression will also be studied. The behavioral and endocrine effects of insulin will be studied in normal subjects and schizophrenic patients while hypoglycemia is prevented by glucose administration. These studies are prompted in part by recent observations that not all endocrine effects of insulin are due to hypoglycemia. This broad program of research into the behavioral and predictive properties of peptide hormones in both animals and man will involve a variety of techniques and a number of collaborators skilled in their special application.